tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management
Authors: Dhiraj Tripathi, Thomas Reiberger
Journal: Hepatology (2023)

To the editor, We read with interest the article by Allaire and Thabut on the management of portal hypertension (PH) in patients with HCC.1 We would like to clarify some important aspects of the Baveno VII recommendations2 for starting nonselective beta-blockers (NSBBs). The authors correctly mentioned that Baveno VII focuses on clinically significant portal hypertension (CSPH) to select patients with compensated advanced chronic liver disease for NSBB regardless of varices.3,4 Evidence supports using liver stiffness measurement (LSM) ≥25 kPa through vibration-controlled transient elastography as a CSPH surrogate in patients with hepatitis C or hepatitis B infection, or alcohol-associated liver disease, and nonobese NASH—but not for other etiologies or for obese NASH. However, the PREDESCI trial3 showed LSM to be a flawed predictor of decompensation (optimal LSM cutoff at 22 kPa). Moreover, LSM is subject to confounders, which can result in falsely elevated results.5 As mentioned by the authors, in patients with HCC, the tumor mass can also lead to imprecise LSM, impacting its correlation with HVPG, and LSM could rule in or rule out CSPH in only half of the real-world cases. Vibration-controlled transient elastography-LSM is likely to be of limited value in patients with HCC when the technique seems so inefficient. In contrast to author’s advice, we would not recommend selecting patients with HCC for NSBB solely based on LSM criteria for CSPH without an endoscopy (Figure 2 in the original manuscript), since (outside of HCC) the benefit of NSBB was only seen in patients with varices.3,4 Baveno VII does not universally recommend NSBB for all patients with compensated advanced chronic liver disease with LSM ≥25 kPa, and in HCC, this strategy seems particularly problematic. The only evidence for starting NSBB without an endoscopy is if CSPH is confirmed by a baseline HVPG ≥10 mm Hg. In conclusion, we agree that sufficient treatment of CSPH improves the survival of patients with HCC. However, we advise caution in deciding to start NSBB in all patients with compensated cirrhosis (regardless of HCC) if CSPH diagnosis is based only on vibration-controlled transient elastography-LSM ≥25 kPa. We would strongly recommend a position of clinical equipoise and wait for the evidence to be generated for this strategy.
ASCO Ethical Guidance for the US Oncology Community Where Reproductive Health Care Is Limited by Law
Authors: Rebecca A. Spence, Leslie J. Hinyard, Reshma Jagsi, Rachel B. Jimenez, Ana Maria Lopez, Mariana Chavez-MacGregor, Kayte Spector-Bagdady, Abby R. Rosenberg
Journal: Journal of Clinical Oncology (2023)

The decision in Dobbs v Jackson Women's Health Organization overturned federal protections for abortion rights, making way for states to enact abortion bans with or without exceptions for the health or life of the pregnant patient. Patient care across many areas of medicine including oncology continues to be affected. Although the change in the legal landscape is widely felt, the core ethical considerations for physicians do not change because of restrictions on the practice of medicine. ASCO offers this guidance to assist US oncologists and institutions who must balance limitations with established ethical duties. This paper articulates principles for cancer care and pregnancy, offers a framework for ethical reflection and action for oncologists who care for pregnant patients, and makes recommendations for individual and institutional action to support evidence-based, patient-centered care in the United States where abortion is illegal or access is limited.
Assessing Heart Failure vs Lymphoma Treatment Risks and Benefits—It Takes Two to Tango
Authors: Ana Barac
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells
Authors: Naresh Doni Jayavelu, Matthew C. Altman, Basilin Benson, Matthew J. Dufort, Elizabeth R. Vanderwall, Lucille M. Rich, Maria P. White, Patrice M. Becker, Alkis Togias, Daniel J. Jackson, Jason S. Debley
Journal: Journal of Allergy and Clinical Immunology (2023)
Fraction of Osteocalcin Endothelial Progenitor Cells and Cardiovascular Risk
Authors: Ilke Ozcan, Yoshihisa Kanaji, Arush Rajotia, Takumi Toya, Nadia Akhiyat, David Morse, Lilach O. Lerman, Amir Lerman
Journal: Circulation Research (2023)

ndothelial progenitor cells (EPCs) play a role in vascular repair, and their levels might represent cardiovascular health. 1 Contrarily, osteocalcin-expressing EPCs (OC-EPCs) have previously been linked to coronary artery disease. 2,3However, their association with cardiovascular risk factors and long-term prognosis is yet to be elucidated.Here, we aimed to investigate this aspect of the EPCs further.Between September 2006 and October 2020, 1046 patients visiting our Cardiology department were enrolled in the prospective research database to enumerate EPCs.The study has been approved by our institutional review board, all patients provided informed consent.Flow cytometry was performed as described previously, 4 cells are presented per 100 000 counts.Laboratory tests were performed around the time of EPC studies.History of diabetes, hypertension, and hyperlipidemia was defined as any previous diagnosis of these conditions in the patient's charts before or at the time of EPC studies.Major adverse cardiovascular event was defined as any stroke, myocardial infarction, heart failure hospitalization, coronary revascularization, and all-cause death.Statistical analyses were performed using JMP or R software in a blinded manner.After excluding patients with inadequate flow cytometry analyses (n=21) and who had acute coronary syndrome on the date of EPC measurement (n=28), a total of 997 patients were included in the analyses.The baseline characteristics are summarized in Figure [A].Median CD34+, CD34+KDR+ (kinase insert domain receptor), and CD34+KDR+OC+ levels were 1010 (610-1530), 70 (20-203), and 14 (1-52) cells per 100 000 counts, respectively.CD34+ cell levels were lower in those with hypertension (940 [540-1490] versus 1040
Targeting tumor vasculature to improve antitumor activity of T cells armed ex vivo with T cell engaging bispecific antibody
Authors: Jeong A Park, Madelyn Espinosa-Cotton, Hong-fen Guo, Sebastien Monette, Nai-Kong V Cheung
Journal: Journal for ImmunoTherapy of Cancer (2023)

Success of T cell immunotherapy hinges on the tumor microenvironment (TME), and abnormal tumor vasculature is a hallmark of most solid tumors and associated with immune evasion. The efficacy of T cell engaging bispecific antibody (BsAb) treatment relies on the successful trafficking and cytolytic activity of T cells in solid tumors. Normalization of tumor vasculature using vascular endothelial growth factor (VEGF) blockades could improve efficacy of BsAb-based T cell immunotherapy.Anti-human VEGF (bevacizumab, BVZ) or anti-mouse VEGFR2 antibody (DC101) was used as VEGF blockade, and ex vivo armed T cells (EATs) carrying anti-GD2, anti-HER2, or anti-glypican3 (GPC3) IgG-(L)-scFv platformed BsAb were used. BsAb-driven intratumoral T cell infiltration and in vivo antitumor response were evaluated using cancer cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) carried out in BALB-Rag2-/-IL-2R-γc-KO (BRG) mice. VEGF expression on human cancer cell lines was analyzed by flow cytometry, and VEGF levels in mouse serum were measured using VEGF Quantikine ELISA Kit. Tumor infiltrating lymphocytes (TILs) were evaluated using flow cytometry and by bioluminescence; both TILs and tumor vasculature were studied using immunohistochemistry.VEGF expression on cancer cell lines increased with seeding density in vitro. BVZ significantly reduced serum VEGF levels in mice. BVZ or DC101 increased high endothelial venules (HEVs) in the TME and substantially enhanced (2.1-8.1 fold) BsAb-driven T cell infiltration into neuroblastoma and osteosarcoma xenografts, which was preferential for CD8(+) TILs versus CD4(+) TILs, leading to superior antitumor effects in multiple CDX and PDX tumor models without added toxicities.VEGF blockade using specific antibodies against VEGF or VEGFR2 increased HEVs in the TME and cytotoxic CD8(+) TILs, significantly improving the therapeutic efficacy of EAT strategies in preclinical models, supporting the clinical investigation of VEGF blockades to further enhance BsAb-based T cell immunotherapies.
Stroke, Myocardial Infarction, and Pulmonary Embolism after Bivalent Booster
Authors: Marie-Joelle Jabagi, Marion Bertrand, Jérémie Botton, Stéphane Le Vu, Alain Weill, Rosemary Dray-Spira, Mahmoud Zureik
Journal: New England Journal of Medicine (2023)

Pulmonary Embolism after Bivalent BoosterTo the Editor: A bivalent messenger RNA vaccine targeting both the ancestral and omicron BA.4-BA.5 sublineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Pfizer-BioNTech) was introduced in France in early October 2022 and recommended for booster vaccination in vulnerable populations.Between October 6 and November 9, both monovalent and bivalent vaccines were available for administration to persons who were 50 years of age or older.In January 2023, the Vaccine Safety Datalink of the Centers for Disease Control and Prevention alerted the public about a possible increased risk of ischemic stroke within the 21 days after the bivalent injection in persons 65 years of age or older. 1 We previously found no increase in the incidence of stroke, acute myocardial infarction, or pulmonary embolism after administration of the monovalent vaccine. 2,3Thus, we wanted to assess whether the risk of such events differed after receipt of the bivalent booster as compared with the monovalent booster.In this population-based study, we used comprehensive data from the French National Health Data System linked to the national coronavirus disease 2019 (Covid-19) vaccination database.All persons who were 50 years of age or older and who had received a booster dose between October 6 and November 9, 2022, were included in the study.This time window captured the only period in which both vaccines were being administered in France.During this period, the uptake of the bivalent vaccine overtook the uptake of the monovalent vaccine, with 932,583 persons receiving the bivalent vaccine and 121,362 receiving the monovalent vaccine (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).
Addressing Size-Based Disparities in Liver Transplant
Authors: Angela L. Hill, William C. Chapman
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Engineering self-healing adhesive hydrogels with antioxidant properties for intrauterine adhesion prevention
Authors: Luyao Feng, Liqun Wang, Yao Ma, Wanglin Duan, Sergio Martin-Saldaña, Ye Zhu, Xianpeng Zhang, Bin Zhu, Chaowei Li, Shibo Hu, Mingjie Bao, Ting Wang, Yuan Zhu, Fei Yang, Yazhong Bu
Journal: Bioactive Materials (2023)

Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.
Vedolizumab for the Treatment of Chronic Pouchitis
Authors: Simon Travis, Mark S. Silverberg, Silvio Danese, Paolo Gionchetti, Mark Löwenberg, Vipul Jairath, Brian G. Feagan, Brian Bressler, Marc Ferrante, Ailsa Hart, Dirk Lindner, Armella Escher, Stephen Jones, Bo Shen
Journal: New England Journal of Medicine (2023)

Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).
Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes
Authors: Sung-Eun Lee, Feng Wang, Maison Grefe, Abel Trujillo-Ocampo, Wilfredo Ruiz-Vasquez, Koichi Takahashi, Hussein A. Abbas, Pamella Borges, Dinler Amaral Antunes, Gheath Al-Atrash, Naval Daver, Jeffrey J. Molldrem, Andrew Futreal, Guillermo Garcia-Manero, Jin S. Im
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA). Experimental Design: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment. Results: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape. Conclusions: Analysis of tumor–immune landscape in MDS during immunotherapy provides clinical response biomarkers.
Acute rejection after liver transplantation with machine perfusion versus static cold storage: A systematic review and meta-analysis
Authors: Marianna Maspero, Khaled Ali, Beatrice Cazzaniga, Sumeyye Yilmaz, Roma Raj, Qiang Liu, Cristiano Quintini, Charles Miller, Koji Hashimoto, Robert L. Fairchild, Andrea Schlegel
Journal: Hepatology (2023)

Background and Aims: Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33–0.91), p =0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29–1), p =0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20–0.91) p =0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14–1), p =0.05]. Conclusions: Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.
Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment
Authors: Christine McInnis, Shilpa Bhatia, Brinda Vijaykumar, Qiaomu Tian, Yanbo Sun, Del Leistritz-Edwards, Charles T Quinn, Ravi Uppaluri, Ann Marie Egloff, Lakshmi Srinivasan, Daniel C Pregibon, Anthony J Coyle, Glenn J Hanna
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background High-risk human papillomavirus (HPV) is a primary cause of an increasing number of oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology of these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with cancers without viral components. However, specific virally-encoded epitopes and their corresponding immune responses are not fully defined. Methods To understand the OPSCC immune landscape, we conducted a comprehensive single-cell analysis of HPV16+ and HPV33+ primary tumors and metastatic lymph nodes. We used single-cell analysis with encoded peptide-human leukocyte antigen (HLA) tetramers to analyze HPV16+ and HPV33+ OPSCC tumors, characterizing the ex vivo cellular responses to HPV-derived antigens presented in major Class I and Class II HLA alleles. Results We identified robust cytotoxic T-cell responses to HPV16 proteins E1 and E2 that were shared across multiple patients, particularly in HLA-A*01:01 and HLA-B*08:01. Responses to E2 were associated with loss of E2 expression in at least one tumor, indicating the functional capacity of these E2-recognizing T cells and many of these interactions validated in a functional assay. Conversely, cellular responses to E6 and E7 were limited in quantity and cytotoxic capacity, and tumor E6 and E7 expression persisted. Conclusions These data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies.
Tickborne Diseases
Authors: Alison E. Burke, Kimberly Knoper, Emily Ling, Robert P. Smith, Darren Taichman, Sam R. Telford
Journal: New England Journal of Medicine (2023)

In this Double Take video from the New England Journal of Medicine, Sam Telford and Robert Smith provide a clinical overview of the various tickborne diseases commonly encountered across the United States, including Lyme disease, babesiosis, and anaplasmosis, among others. Starting with characteristics of ticks and their ability to act as disease vectors, the video reviews the clinical presentation of these infections, clues on physical examination, and laboratory tests to consider when encountering a patient with a potential tickborne infection.